Pfizer Inc. (NYSE: PFE)today presented results from the Phase 3 BASIS study (NCT03938792) evaluating HYMPAVZI® (marstacimab) for adults and adolescents living with hemophilia A or B with inhibitors. The results demonstrated the superiority of HYMPAVZI in improving key bleeding outcomes compared to on-demand (OD) treatment with bypassing agents. HYMPAVZI was administered with a straightforward, once-weekly subcutaneous injection requiring minimal preparation and no treatment-related lab monitoring.
The findings were shared today in an oral presentation at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando and published in Blood.
Inhibitors, or antibodies, which neutralize factor replacement therapies and render them ineffective, may develop in people living with hemophilia.1 Inhibitors can be diagnosed with a blood test.2 Of the more than 800,000 people in the world living with hemophilia A or hemophilia B, approximately 20% of people with hemophilia A and 3% of people with hemophilia B are unable to continue taking factor replacement therapies because they develop inhibitors to FVIII (factor VIII) and FIX (factor IX), respectively, and these therapies no longer prevent or stop bleeding episodes.2,3
"The emergence of inhibitors poses significant treatment challenges and can increase disease burden for people living with hemophilia A or B,"4 said Davide Matino, M.D., M.Sc., BASIS Principal Investigator, Associate Professor of Medicine, McMaster University. "In patients with inhibitors, this study demonstrates HYMPAVZI's potential as a safe and efficacious treatment option that not only significantly reduced bleeding episodes via a once-weekly subcutaneous administration, but also demonstrated improvement in certain aspects of health-related quality of life."
In the BASIS trial, 48 adults and adolescents living with severe hemophilia A or hemophilia B with inhibitors were treated with HYMPAVZI during the 12-month active treatment phase (ATP) following a preceding OD intravenous regimen with bypassing agents, administered as part of usual care in a six-month observational phase. During the ATP, participants received HYMPAVZI as a 300 mg subcutaneous loading dose, followed by once-weekly 150 mg dosing. The study found:
- A statistically significant and clinically meaningful 93% reduction in mean treated annualized bleeding rate (ABR) (1.39 [95% CI: 0.85-2.29] vs.19.78 [95% CI: 16.12-24.27]; p<0.0001), demonstrating superiority of HYMPAVZI over OD therapy.
- These results were consistent across hemophilia type, age, and geographies.
- Additionally, a median ABR of 0 (95% CI: 0.00-14.91) was observed with HYMPAVZI compared to 16.42 (95% CI: 0.00-69.10) with OD treatment.
- Superiority (p<0.0001) of HYMPAVZI was also demonstrated across all bleeding-related secondary endpoints - spontaneous bleeds (ABR 0.87 vs. ABR OD 15.27), joint bleeds (ABR 1.10 vs. ABR OD 15.15), target joint bleeds (ABR 0.79 vs. ABR OD 6.42), and total treated and untreated bleeds (ABR 4.36 vs. ABR OD 27.29).
- After six months in the ATP, HYMPAVZI demonstrated superiority and/or numerical improvement on health-related quality-of-life outcomes compared to OD therapy, via:
- A median difference of -25.9 (95% CI: ‑37.5 to -14.2; p<0.0001) in the Haem-A-QoL physical health domain (assessed patient-reported physical burden of disease such as joint and swelling pain, difficulty moving, and time to get ready),
- A median difference of -13.5 (95% CI: -19.8 to -7.2; p<0.0001) in the Haem-A-QoL total score (assessed patient-reported outcomes across 10 domains related to health-related quality of life and daily activities),
- A median difference of 0.1043 (95% CI: 0.0060 to 0.2027; p<0.0377) in the EQ-5D-5L (assessed patient-reported outcomes related to mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) index score.
- A median difference of 7.5 (95% CI: -1.9 to 17.0) in the EQ-VAS score (a component of the EQ-5D-5L and overall rating of a patient's self-reported health).
HYMPAVZI was generally well tolerated. No deaths or thromboembolic events were reported in the 51 participants included in the safety population. Thirty-eight patients reported adverse events (AEs) during the ATP and the most common were COVID-19 (21.6%), upper respiratory tract infection (15.7%), fibrin D-dimer increase (9.8%), and headache (9.8%). Most AEs were mild or moderate in severity. During the ATP, one patient reported a serious AE (skin rash). The serious AE was treatment related and led to study discontinuation, and was resolved.
"It is encouraging that these data demonstrate the potential of HYMPAVZI to combine efficacy, safety, and straightforward administration for adults and adolescents living with hemophilia A or B with inhibitors and address a significant patient need," said Michael Vincent, M.D., Ph.D., Chief Inflammation & Immunology Officer, Pfizer. "We look forward to potentially making this treatment available for these patients as Pfizer continues its ongoing effort spanning more than 40 years to improve hemophilia care."
Pfizer has submitted these data to the U.S. Food and Drug Administration and European Medicines Agency for review.
HYMPAVZI is currently approved in more than 40 countries for the treatment of eligible patients 12 years of age and older living with hemophilia A without factor VIII inhibitors, or hemophilia B without factor IX inhibitors.
About the BASIS study
The pivotal BASIS study is a global Phase 3, open-label, multicenter study to evaluate the efficacy data and safety profile of HYMPAVZI in adolescent and adult participants ages 12 to <75 years with severe hemophilia A (defined as FVIII <1%) or moderately severe to severe hemophilia B (defined as FIX activity ≤2%) with or without inhibitors.
This cohort included 48 people living with hemophilia with inhibitors who were treated with HYMPAVZI during a 12-month active treatment period (ATP) versus an on-demand intravenous regimen with bypassing agents, administered as part of usual care in a six-month observational period. During the ATP, participants received prophylaxis (a 300 mg subcutaneous loading dose of HYMPAVZI, followed by 150 mg subcutaneously once weekly) with potential for dose escalation to 300 mg once weekly. An additional three patients in the inhibitor cohort were on routine prophylactic treatment prior to the study and not included in the primary efficacy analysis.
